Background: Identifying what therapies constitute complementary, alternative, and/or integrative medicine (CAIM) is complex for a multitude of reasons. An operational definition is dynamic, and changes based on both historical time period and geographical location whereby many jurisdictions may integrate or consider their traditional system(s) of medicine as conventional care. To date, only one operational definition of “complementary and alternative medicine” has been proposed, by Cochrane researchers in 2011. This definition is not only over a decade old but also did not use systematic methods to compile the therapies. Furthermore, it did not capture the concept “integrative medicine”, which is an increasingly popular aspect of the use of complementary therapies in practice. An updated operational definition reflective of CAIM is warranted given the rapidly increasing body of CAIM research literature published each year. Methods: Four peer-reviewed or otherwise quality-assessed information resource types were used to inform the development of the operational definition: peer-reviewed articles resulting from searches across seven academic databases (MEDLINE, EMBASE, AMED, PsycINFO, CINAHL, Scopus and Web of Science); the “aims and scope” webpages of peer-reviewed CAIM journals; CAIM entries found in online encyclopedias, and highly-ranked websites identified through searches of CAIM-related terms on HONcode. Screening of eligible resources, and data extraction of CAIM therapies across them, were each conducted independently and in duplicate. CAIM therapies across eligible sources were deduplicated. Results: A total of 101 eligible resources were identified: peer-reviewed articles (n = 19), journal “aims and scope” webpages (n = 22), encyclopedia entries (n = 11), and HONcode-searched websites (n = 49). Six hundred four unique CAIM terms were included in this operational definition. Conclusions: This updated operational definition is the first to be informed by systematic methods, and could support the harmonization of CAIM-related research through the provision of a standard of classification, as well as support improved collaboration between different research groups.

The definition of complementary, alternative, and integrative medicine (CAIM) remains dynamic and complex despite a steady increase in the popularity/usage of CAIM therapies across the globe. A lack of consistency in how these terms are defined remains a challenge for researchers, clinicians, and national and international organizations (e.g., World Health Organization, National Center for Complementary and Integrative Health) alike. In the present article, we provide a brief history of the use of these terminologies, and then outline the process we took to develop and create an operational definition of complementary, alternative, and integrative medicine. Our operational definition is the first to be informed by a systematic search of four quality-assessed information resource types, ultimately yielding 604 unique CAIM therapies. We then developed a single search string for the most common bibliographic databases using the finalized operational definition list of CAIM therapies. These CAIM therapies were searched against the Therapeutic Research Center's “Natural Medicines” database for all 604 therapies, whereby each item's scientific name and/or synonym was included as a keyword or phrase in the search string. While the current definition is not without limitations and ongoing debates still surround the field, this work is arguably a steppingstone towards enabling increased collaboration and communication amongst healthcare clinicians, researchers, and the public. This operational definition provides a foundation for developing well-coordinated research efforts that will assist in the acceptance and understanding of this field, while also focusing on adopting knowledge translation techniques and efforts for further research advancement and use.

Herpes simplex virus type 2 (HSV-2) is the primary cause of genital herpes which results in significant morbidity and mortality, especially in women, worldwide. HSV-2 is transmitted primarily through infection of epithelial cells at skin and mucosal surfaces. Our earlier work to examine interactions between HSV-2 and vaginal epithelial cells demonstrated that infection of the human vaginal epithelial cell line (VK2) with HSV-2 resulted in increased expression of TRIM26, a negative regulator of the Type I interferon pathway. Given that upregulation of TRIM26 could negatively affect anti-viral pathways, we decided to further study the role of TRIM26 in HSV-2 infection and replication. To do this, we designed and generated two cell lines derived from VK2s with TRIM26 overexpressed (OE) and knocked out (KO). Both, along with wildtype (WT) VK2, were infected with HSV-2 and viral titres were measured in supernatants 24 h later. Our results showed significantly enhanced virus production by TRIM26 OE cells, but very little replication in TRIM26 KO cells. We next examined interferon-β production and expression of two distinct interferon stimulated genes (ISGs), MX1 and ISG15, in all three cell lines, prior to and following HSV-2 infection. The absence of TRIM26 (KO) significantly upregulated interferon-β production at baseline and even further after HSV-2 infection. TRIM26 KO cells also showed significant increase in the expression of MX1 and ISG15 before and after HSV-2 infection. Immunofluorescent staining indicated that overexpression of TRIM26 substantially decreased the nuclear localization of IRF3, the primary mediator of ISG activation, before and after HSV-2 infection. Taken together, our data indicate that HSV-2 utilizes host factor TRIM26 to evade anti-viral response and thereby increase its replication in vaginal epithelial cells.

Background: The vaginal microbiome (VMB) is a critical determinant of reproductive health, where a microbial shift towards a dysbiotic environment has implications for susceptibility to, and clinical presentation of sexually transmitted infections (STIs). Metabolomic profiling of the vaginal microenvironment has led to the identification of metabolic responses to clinical conditions of dysbiosis. However, no studies have examined metabolic markers that are common across conditions and can serve as a signature for vaginal dysbiosis.Method of Study: We have conducted a comprehensive systematic review and meta‐analysis to identify consistently deregulated metabolites along with their impact on host and microbial metabolism during dysbiosis. We employed two complementary approaches including a vote counting analysis for all eligible studies identified in the systematic review, in addition to a meta‐analysis for a subset of studies with sufficient available data. Significantly deregulated metabolites were then selected for pathway enrichment analysis.Results: Our results revealed a total of 502 altered metabolites reported across 10 dysbiotic conditions from 16 studies. Following a rigorous, collective analysis, six metabolites which were consistently downregulated and could be generalized to all dysbiotic conditions were identified. In addition, five downregulated and one upregulated metabolite was identified from a bacterial vaginosis (BV) focused sub‐analysis. These metabolites have the potential to serve as a metabolic signature for vaginal dysbiosis. Their role in eight altered metabolic pathways indicates a disruption of amino acid, carbohydrate, and energy metabolism during dysbiosis.Conclusion: Based on this analysis, we propose a schematic model outlining the common metabolic perturbations associated with vaginal dysbiosis, which can be potential targets for therapeutics and prophylaxis.

Journal of Translational Genetics and Genomics is an open access journal, publishing articles related to single gene disorders, rare genetic disease, specific genetic syndromes, complex disease, etc.